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Journal of Virology, March 2007, p. 3005-3008, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02083-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Synergy of Small Molecular Inhibitors of Hepatitis C Virus Replication Directed at Multiple Viral Targets{triangledown}

David L. Wyles,1* Kelly A. Kaihara,1 Florin Vaida,2 and Robert T. Schooley1

Department of Medicine, Division of Infectious Diseases,1 Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, California2

Received 22 September 2006/ Accepted 10 December 2006

Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.

* Corresponding author. Mailing address: 9500 Gilman Drive, MC 0711, La Jolla, CA 92093. Phone: (858) 822-1779. Fax: (858) 822-5362. E-mail: dwyles{at}ucsd.edu.

{triangledown} Published ahead of print on 20 December 2006.

Journal of Virology, March 2007, p. 3005-3008, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02083-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wyles, D. L., Kaihara, K. A., Korba, B. E., Schooley, R. T., Beadle, J. R., Hostetler, K. Y. (2009). The Octadecyloxyethyl Ester of (S)-9-[3-Hydroxy-2-(Phosphonomethoxy) Propyl]Adenine Is a Potent and Selective Inhibitor of Hepatitis C Virus Replication in Genotype 1A, 1B, and 2A Replicons. Antimicrob. Agents Chemother. 53: 2660-2662 [Abstract] [Full Text]  
  • Wyles, D. L., Kaihara, K. A., Schooley, R. T. (2008). Synergy of a Hepatitis C Virus (HCV) NS4A Antagonist in Combination with HCV Protease and Polymerase Inhibitors. Antimicrob. Agents Chemother. 52: 1862-1864 [Abstract] [Full Text]  


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